tbuckley/cabot-search huggingface dataset:
Abstract P2-14-20: Comparison of robot-assisted nipple sparing mastectomy with conventional nipple sparing mastectomy: a single-center experience
Authors: Ji Young You, Haemin Lee, Eun-Shin Lee, Seung Pil Jung
Journal: Cancer Research (2023)

Abstract Purpose: Robot-assisted nipple-sparing mastectomy (RANSM) improves cosmetic outcomes compared to conventional nipple-sparing mastectomy (CNSM) since RANSM is performed with minimal incisions. However, there are few studies on the feasibility and surgical outcome of RANSM. The aim of this study was to compare the surgical outcomes of RANSM and CNSM in breast cancer patients. Method: A retrospective observational study was conducted at our institution between January 2021 and December 2021. A total of 54 patients diagnosed with breast malignancy that underwent either a robotic-assisted or conventional nipple-sparing mastectomy were included. The demographics of the patient’s sex, age, body mass index (BMI), breast weight, and preoperative diagnosis were investigated. The surgical method, operation time (including docking time and console time in the case of robotic surgery), postoperative complications, length of hospital stay, pain score, and adjuvant therapy were analyzed. Result: A total of 57 breasts in 54 female patients were included in the study: 36 invasive ductal carcinoma patients, 11 ductal carcinoma cases, 6 invasive lobular carcinoma, 2 mucinous carcinoma, one solid papillary carcinoma and one lobular carcinoma in situ. A median age of 49(27-66), mean BMI of 22 (18.89-26.28), and mean breast weight was 246 g (120-305g). The mean operation time was 122 minutes (robotic 140 vs. conventional 118), and the average docking time was five minutes and console time 60 minutes in the robot-assisted surgery. There was only one postoperative complication in the robot group and ten cases in the conventional group. The mean hospital stay was 12.6 days (RANSM 10.75 vs. CNSM 12.92), and the average pain score was 3.53 (RANSM 3.50 vs. CNSM 3.54). None needed adjuvant therapy in the robot group. In the conventional surgical group, four patients underwent adjuvant radiotherapy and sixteen patients underwent chemotherapy including six neoadjuvant cases. Conclusion: Our results showed that RANSM had advantages of shorter hospitalization and lower pain scores although it had slightly longer operation time and could not applicable in relatively large breasts. In the near future, RANSM may be considered as the surgery of choice over CNSM in breast cancer patients. Citation Format: Ji Young You, Haemin Lee, Eun-Shin Lee, Seung Pil Jung. Comparison of robot-assisted nipple sparing mastectomy with conventional nipple sparing mastectomy: a single-center experience. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-20.
Abstract P1-04-16: A nomogram based on clinicopathologic factors and pretreatment systemic inflammation response index to predict pathological complete response of neoadjuvant systemic therapy in HER2-positive breast cancer: A dual-center study
Authors: Hong Yu Wu, Yen-Dun Tzeng, Jie Ru Yang, Chih Chiang Hung
Journal: Cancer Research (2023)

Abstract Purpose: Multiple pretreatment systemic inflammatory markers (SIMs) have been reported as predictors of pathological complete response (pCR) after neoadjuvant systemic therapy (NST) in patients with breast cancer (BC). However, the most significant SIM remains to be conclusively identified, and variations among different molecular subtypes remain unknown. The objective of the study was to identify the most significant SIM in patients with human epidermal growth factor receptor 2 (HER2) positive BC, and to construct a pCR-predictive nomogram combining it with other clinicopathological factors. Methods: We retrospectively reviewed the findings for 240 patients with stage I–III HER2-positive BC who underwent NST and subsequent surgery at Kaohsiung and Taichung Veterans General Hospital from 2011 to 2021. Clinicopathological factors were analyzed by stepwise logistic regression with forward selection. The data were used to construct a nomogram plot for determining the probability of pCR. Results: Among the pretreatment SIMs, only SIRI was significantly related to pCR, with an optimal cutoff value of 1.27 × 10^9/L. Stepwise logistic analyses indicated that clinical N stage, HER2 immunohistochemistry (IHC) score, hormone receptor status, targeted therapy regimen, and SIRI were independent predictors of pCR, with an area under the curve (AUC) of 0.722. The Hosmer–Lemeshow test and calibration curve revealed that the predictive ability was a good fit to actual observations. A nomogram was constructed based on the logistic model. Conclusions: Pretreatment SIRI &amp;lt; 1.27 is predictive of pCR in HER2-positive BC. Our nomogram could efficiently predict pCR and facilitate clinical decision-making before neoadjuvant treatment. Univariable and multivariable analyses for predictive factors of pathological complete response of neoadjuvant systemic therapy in HER2-positive breast cancer Citation Format: Hong Yu Wu, Yen-Dun Tzeng, Jie Ru Yang, Chih Chiang Hung. A nomogram based on clinicopathologic factors and pretreatment systemic inflammation response index to predict pathological complete response of neoadjuvant systemic therapy in HER2-positive breast cancer: A dual-center study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-16.
Abstract P2-15-02: Omentum-Lipoaspirate Free-Flap Breast Reconstruction in Women with BMI &amp;lt;25
Authors: Irene L. Wapnir, Monica M. Dua, Yulia Zak, Dung Nguyen
Journal: Cancer Research (2023)

Abstract The Omental Fat-Augmented Free-flap (O-FAFF) is being offered at our institution as an alternative method of breast reconstruction. This novel free-flap construct is ideal for underweight and normal weight women who lack abdominal or other donor tissue, desire to avoid donor site morbidity and/or are averse to implant-based reconstruction. We analyze omentum, mastectomy and final construct weights in women with BMI &amp;lt; 25 kg/m2 who underwent nipple-sparing mastectomies and O-FAFF reconstruction. Methods Operative technical features of women undergoing nipple-sparing mastectomies with immediate O-FAFF breast reconstruction over a 34 month period are included. Steps of the operative procedure are as follows: laparascopic omentectomy, liposuction and unilateral or bilateral mastectomy is performed. An acellular dermal matrix (ADM) shell is fashioned around a tissue expander. This mold is filled with the omentum and then engrafted with lipoaspirate followed by microsurgical anastomoses of gastroepiploic artery and vein to internal mammary artery and vein. Weight of biological construct is compared to native breast weight. Results 26 women with average BMI 21.2 kg/m2 underwent unilateral (15) or bilateral (11) nipple-sparing mastectomies and O-FAFF reconstruction. Average omentum weight for 37 breasts was 149 gm (82- 262) and average mastectomy weighed 212.4 gm (85 – 396). The ratio of engrafted fat to omentum weight was 0.73 for unilateral versus 0.91 for bilateral cases. The ratio of omentum-fat graft construct to mastectomy weight was 1.24 for unilateral and 0.96 for bilateral cases. Conclusion O-FAFF is a novel procedure for autologous tissue breast reconstruction after nipple-sparing mastectomy in underweight and normal weight women. Comparable weight replacement for extirpated native breast is achieved. Citation Format: Irene L. Wapnir, Monica M. Dua, Yulia Zak, Dung Nguyen. Omentum-Lipoaspirate Free-Flap Breast Reconstruction in Women with BMI &amp;lt;25 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-15-02.
Abstract P1-13-04: Potentiating Alpelisib in PI3K Pathway Overactive Triple Negative Breast Cancers
Authors: David Boyd, Chuck Harrell
Journal: Cancer Research (2023)

Abstract Potentiating Alpelisib in PI3K Pathway Overactive Triple Negative Breast Cancers David C. Boyd1,2, Amy L. Olex3, Tess Leftwich1, Nicole Hairr1, Alex K. Duong1, Narmeen S. Rashid1,3, Mohammad A Alzubi1,2, Holly Byers1, Aaron D. Valentine1, Julia E. Altman1, Emily Zboril1, Jacqueline M. Grible1, Madelyn Esquivel1, Scott A. Turner1, Andrea Ferreira-Gonzalez1, Mikhail G. Dozmorov5, J. Chuck Harrell1,2,6 1Department of Pathology, Virginia Commonwealth University; 2Integrative Life Sciences Program, VCU; 3Wright Center for Clinical and Translational Research, VCU; 4Department of Biology, University of Richmond; 5Department of Biostatistics, VCU; 6Massey Cancer Center, VCU. There is an urgent need for new therapeutic options for basal-like Triple Negative Breast Cancers (TNBC). To mirror the NCI-ComboMATCH study, and identify new synergistic drug combinations, we analyzed a set of 20 breast cancer patient-derived xenografts and 14 cell lines to identify targetable targets in each model. The Oncomine Comprehensive Assay v3 was performed to assess 161 genes for hotspot mutations, focal copy number variants, amplification/deletions, and RNA-fusion genes. Next, each PDX and their isogenic drug-resistant sublines were analyzed with bulk RNA-sequencing (217 samples) and cell single-cell RNA-sequencing (~100,000 cells). Of all NCI-MATCH defined targetable mutations, 37% of the models contained pathogenic PIK3CA amplifications or mutations. PIK3CA is one of the most common oncogenic aberrations identified in patients and the PI3K pathway is overactive in the majority of TNBCs, therefore we sought to target it across all models and identify the most efficacious synergistic drug partner. Short-term cultures of each PDX model were screened with a library of &amp;gt;1,000 FDA-approved/experimental drugs to identify compounds that were cytotoxic. Synergistic drug screens were then performed with each drug in combination with the PI3K inhibitor byl-719 (alpelisib) a current standard-of-care drug used for PI3K mutant ER+ disease. Synergism was identified using coefficient of drug interaction (CDI) calculations and 10 drugs were identified as synergistic across several models. Using several criteria, including clinical status and pathway analysis, 3 drugs were selected for CompuSyn-based synergism testing and each was confirmed to be synergistic in vitro. Testing with in vivo models of each drug combination has thus far confirmed that each is synergistic per CDI metrics. Those combinations are currently being tested for efficacy in the metastatic setting with a set of basal-like PDXs. Citation Format: David Boyd, Chuck Harrell. Potentiating Alpelisib in PI3K Pathway Overactive Triple Negative Breast Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-04.
Abstract P1-04-12: Systemic immune response to a Phase I/II trial of Durvalumab concomitant with neoadjuvant chemotherapy in early stage TNBC
Authors: Kim Blenman, Michal Marczyk, Julia Foldi, Vignesh Gunasekharan, Andrea L.M. Silber, Lajos Pusztai
Journal: Cancer Research (2023)

Abstract Background Peripheral blood cells and secreted products are important regulators of the systemic immune response. Circulating cytokines have been shown to predict severity of immune-related toxicity in melanoma patients that received combination anti-PD-1-based immunotherapy. In this study, we evaluated 38 serum cytokines and the peripheral blood t cell receptor (TCR) immune repertoire of 66 patients with TNBC for associations with pCR, treatment phase (PRE; POST), and immune related treatment emergent adverse events (TEAEs). Methods Serum and peripheral blood buffy coats were collected at pre-treatment (week 0) and at post-treatment (~ week 24). MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel was run in duplicate and read on the Luminex platform. Genomic DNA was isolated using QIAGEN Kits per manufacturer’s instructions. TCR immune repertoire profiling was performed using the Immunoseq at Adaptive Biotechnologies. Statistical analysis was performed in R. P-values &amp;lt; 0.05 for serum cytokines and P-values &amp;lt; 0.05 for TCR were considered significant. Results Pielou’s diversity index showed no difference between patient groups for TCR (P&amp;gt;0.319). Baseline samples had increased sCD40L, EGF, and IL-10 in patients with RD compared to pCR (P&amp;lt; 0.05). Baseline samples had decreased FGF2 and IFN gamma in patients with immune related TEAEs compared to those with no immune related TEAEs (P&amp;lt; 0.05). Comparison of Pre- vs Post-treatment revealed that EGF, MIP1 alpha, IL-1 alpha, IL-8, and MDC were increased in patients with pCR compared to those with RD. Comparison of Pre- vs. Post- also revealed increased levels of cytokines (EGF, IL-7, IFN gamma, GM-CSF) in samples in patients with immune related TEAEs (P&amp;lt; 0.05) compared to those patients without immune-related TEAEs. It also revealed that there was an increase in a subset of cytokines (IL-7, IL-4, MCP3, and IL-1 alpha) in patients that presented with serious immune related TEAEs (P&amp;lt; 0.05) compared to those patients without serious immune-related TEAEs. Conclusions There are subsets of circulating inflammatory cytokines that may be associated with treatment emergent adverse events in patients with TNBC treated with Durvalumab concomitant with standard of care chemotherapy. Citation Format: Kim Blenman, Michal Marczyk, Julia Foldi, Vignesh Gunasekharan, Andrea L.M. Silber, Lajos Pusztai. Systemic immune response to a Phase I/II trial of Durvalumab concomitant with neoadjuvant chemotherapy in early stage TNBC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-12.
Abstract P1-10-14: Higher radiation dose to the heart in left sided breast cancer; anatomy versus dosimetry
Authors: Mohamed Alm El-Din, Andrzej Niemierko, Alphonse Taghian
Journal: Cancer Research (2023)

Abstract Abstract: Background: There is assumption that omitting the internal mammary chain radiotherapy (IMC RT) in patients with breast cancer (BC) will significantly reduce the cardiac exposure for all patients regardless the cardiac anatomy of each patient. Aim: to evaluate the impact of IMC RT on the dose received by the heart and its chambers in patients with favorable versus unfavorable cardiac anatomy. Patients and methods: CT scans were obtained of 20 patients with left-sided BC, 10 with favorable and 10 with unfavorable cardiac anatomy. Three plans were generated for each patient, one treating only the breast with tangents, and one treating the breast and IMC with wide photon tangents, and one treating the breast and IMC to 50Gy with photon tangent fields and a matching medial electron field. Dose volume histograms (DVHs) were generated for the heart and chambers. The equivalent uniform doses (EUDs) were calculated for each DVH, and the mean EUDs for plans with unfavorable and favorable cardiac anatomy were compared using a two-sided two-sample T-test Results: The mean dose received by the heart from plans with tangents plus IMC fields in patients with favorable cardiac anatomy was significantly lower than that received from plans with tangents only or wide tangents in patients with unfavorable anatomy (P &amp;lt; .0001). The average EUD for plans with tangents and IMC fields in the favorable group was 16 Gy (SD = 4.5) as compared to 36 Gy (SD = 3.6) and 37 Gy (SD = 5.1) for plans with tangents only and wide tangents in the unfavorable group, respectively ((P &amp;lt; .0001). The doses to the right ventricle were not significantly different. Conclusions: Ttreatment plans should be individualized based on the cardiac anatomy of each patient. Citation Format: Mohamed Alm El-Din, Andrzej Niemierko, Alphonse Taghian. Higher radiation dose to the heart in left sided breast cancer; anatomy versus dosimetry [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-14.
Abstract P2-16-03: The Speckle-type POZ protein (SPOP) inhibits breast cancer malignancy by destabilizing oncogene TWIST1
Authors: Chunli Wei, Yun Liu, Xiaoyan Liu, Jingliang Cheng, Jiewen Fu, Xiuli Xiao, Robb E Moses, Xiaotao Li, Junjiang Fu
Journal: Cancer Research (2023)

Abstract Epithelial-mesenchymal transition (EMT) inducing transcription factor TWIST1 plays a vital role in cancer metastasis. How the tumor-suppressive E3 ligase, Speckle-type POZ protein (SPOP), regulates TWIST1 in breast cancer remains unknown. In this study, we report that SPOP physically interacts with, ubiquitinates, and destabilizes TWIST1. SPOP promotes K63-and K48-linked ubiquitination of TWIST1, predominantly at K73, thereby suppressing cancer cell migration and invasion. Silencing SPOP significantly enhances EMT, which accelerates breast cancer cell migration and invasiveness in vitro and lung metastasis in vivo. Clinically, SPOP is negatively correlated with the levels of TWIST1 in highly invasive breast carcinomas. Reduced SPOP expression, along with elevated TWIST1 levels, is associated with poor prognosis in advanced breast cancer patients, particularly those with metastatic triple-negative breast cancer (TNBC). Taken together, we have disclosed a new mechanism linking SPOP to TWIST1 degradation. Thus SPOP may serve as a prognostic marker and a potential therapeutic target for advanced TNBC patients. Citation Format: Chunli Wei, Yun Liu, Xiaoyan Liu, Jingliang Cheng, Jiewen Fu, Xiuli Xiao, Robb E Moses, Xiaotao Li, Junjiang Fu. The Speckle-type POZ protein (SPOP) inhibits breast cancer malignancy by destabilizing oncogene TWIST1 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-16-03.
Abstract P1-09-02: Oncological, Cosmetic and Quality of life outcomes following breast conservation surgery in patients presenting after non-oncological excsion of breast primary: A prospective follow up study
Authors: R N NAGA SANTOSH IRRINKI, SIDDHANT KHARE, gurpreet Singh, ishita laroiya, aniket mishra
Journal: Cancer Research (2023)

Abstract Background For early-stage breast cancer BCS followed by radiation therapy has been validated as safe alternative to Radical Mastectomy. One peculiar problem faced in developing countries is patients in whom primary tumor has been excised elsewhere. There is a lack of clear treatment history and pre-operative examination and imaging in such patients, which makes accurate staging and planning for definitive surgery much more challenging. We did this retrospective analysis to assess clinical, cosmetic and QOL outcomes in the above-mentioned group of patients. Methods Patients between 18 and 80 years diagnosed with biopsy proven carcinoma breast that had the primary tumor excised outside and underwent BCS at our institute were included. They were subjected to routine history and physical examination as per the institute standard of care. Overall survival was estimated using Kaplan Meier curve. Expected 4 years survival was calculated using percentage of people who were alive out of those patients whose follow up was known at the end of 4 years. Cosmetic outcome was assessed using patient reported BCTOS 12 scores whereas quality of life outcome was assessed using patient reported EORTC and SF 36 questionnaire scores. Results Twenty-two patients were enrolled. Overall survival at 4 years was 72% comparable in NACT and No NACT (p&amp;lt; 0.29). 5.45% patients had local recurrence. Cosmetic outcome was excellent to good in 90% patients, similar between NACT and No NACT (p 0.69). Quality of life was excellent-good in 65% patients (EORTC) which was significantly higher in No NACT group (p 0.05) Conclusion BCS after scar excision following non oncological resection of breast primary may be an acceptable modality of treatment with good cosmetic and Quality of life outcomes. Citation Format: R N NAGA SANTOSH IRRINKI, SIDDHANT KHARE, gurpreet Singh, ishita laroiya, aniket mishra. Oncological, Cosmetic and Quality of life outcomes following breast conservation surgery in patients presenting after non-oncological excsion of breast primary: A prospective follow up study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-02.
Abstract P1-07-07: Cross-talk of Four Types of RNA Modification Proteins with Adenosine Reveals the Landscape of Multivariate Prognostic Patterns in Breast Cancer
Authors: Xuliren Wang, Min Xiong, Bingqiu Xiu, Jiong Wu, Yayun Chi
Journal: Cancer Research (2023)

Abstract Background: BRCA is the most common malignant tumour, and its heterogeneity is one of its major characteristics. m6A, m1A, APA, and A-to-I RNA editing constitute the four most common adenosine-associated RNA modifications and represent the most typical and critical forms of epigenetic regulation contributing to the immunoinflammatory response, tumorigenesis and tumour heterogeneity. However, the cross-talk and potential combined profiles of these RMPs in multivariate prognostic patterns of BRCA remain unknown. Methods: A total of 48 published RMPs were analysed and found to display significant expression alterations and genomic mutation rates between tumour and normal tissues in the TCGA-BRCA cohort. Data from 4188 BRCA patients with clinical outcomes were downloaded from the GEO, METABRIC and TCGA databases, normalized and merged into one cohort. The prognostic value and interconnections of these RMPs were also studied. The four PRGs with the greatest prognostic value were then selected to construct diverse RMP-associated prognostic models through uniCox, differential expression analysis, LASSO regression and multiCox. Alterations in biological functional pathways, genomic mutations, immune infiltrations, RNAss scores and drug sensitivities among different models, as well as their prognostic value, were then explored. Results: Utilizing a large number of samples and a comprehensive set of genes contributing to adenosine-associated RNA modification, our study revealed the joint potential bio-functions and underlying features of these diverse RMPs and provided effective models (PRG clusters, gene clusters and the risk model) for predicting the clinical outcomes of BRCA. The individuals with higher risk scores showed poor prognoses, cell cycle function enrichment, upregulation of stemness scores, higher TMBs, immune activation and specific drug resistance. This work highlights the significance of comprehensively examining post-transcriptional RNA modification genes. Conclusions: Here, we designed and verified an advanced forecasting model to reveal the underlying links between BRCA and RMPs and precisely predict the clinical outcomes of multivariate prognostic patterns for individuals. Citation Format: Xuliren Wang, Min Xiong, Bingqiu Xiu, Jiong Wu, Yayun Chi. Cross-talk of Four Types of RNA Modification Proteins with Adenosine Reveals the Landscape of Multivariate Prognostic Patterns in Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-07-07.